Nanotechnology: Detection & Analysis of Plaque Formation


Project Number

HL080711

Active Period

Current PEN          2005-2010

Web Site

Budget

$11.5 Million ca.

Consortuim

Georgia Institute of Technology
Emory University

Principal Investigator

Gang Bao, Ph.D.
Robert A. Milton Chair in Biomedical Engineering
College of Engineering Distinguished Professor
Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology
M Building - 4100M
Atlanta, GA 30332-0535
phone: 404-385-0373
fax: 404-385-3856
gang.bao@bme.gatech.edu


Aims

This PEN application aims to establish a highly collaborative and multidisciplinary Program of Excellence in Nanotechnology by integrating the bioengineering expertise of Georgia Tech (Atlanta, GA) and the cardiology strengths of Emory University School of Medicine (Atlanta, GA). The broad and long-term goal of this PEN is to develop nanotechnology and biomolecular engineering tools and methodologies for the detection and molecular analysis of atherosclerotic plaque formation, which has a compelling medical need. Cardiovascular disease remains the leading cause of death in the United States: One out of every four Americans has cardiovascular disease, and every 30 seconds one person dies from this disease. Although significant advances have been made in the management and treatment of this disease, there is still a lack of understanding of the fundamental biology and pathophysiology of atherosclerosis, especially the molecular mechanisms responsible for plaque formation. As a result, early detection of atherosclerotic plaque is difficult, leading to a high rate of morbidity and mortality. We propose to develop advanced nanotechnologies for molecular analysis of plaque formation and sensitive detection of plaques. Specifically: (1) we will develop the molecule beacon based technology for mRNA expression and localization in living cells in response to shear stress; (2) we will develop quantum dot (Qd) based probes for studying protein interactions in cells; (3) the QD probes will be further developed for in vivo detection and analysis of plaques; (4) we will develop magnetic nanoparticle probes for in vivo plaque detection; (5) we will carry out a pilot project to develop LDL and chymase based contrast agent for in vivo plaque detection; (6) as a second pilot project we will develop activatable probes for detecting oxidative stress in living cells.

There are six specific aims for this project:

Specific Aim #1: Design, development and optimization of nanostructured probes for specific detection of mRNA in living cells to study molecular mechanisms of atherogenesis

Specific Aim #2: Development of bioconjugated quantum dot probes for protein localization and assembly of signaling complexes in vascular cells

Specific Aim #3: Development of quantum dot based probes for detection and evaluation of atherosclerotic disease

Specific Aim #4: Development of magnetic nanoparticle-based probes for plaque detection using MRI

Specific Aim #5: LDL and chymase based contrast agent for in vivo plaque detection

Specific Aim #6: Activatable probes for sensitive detection of oxidative stress in living cells

 


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